Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome.

The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31-164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11-42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6-14.8 versus 1.1 U/ml; range 0.4-3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0. 6-11.4 versus 0.46 U/ ml; range 0.00-1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45-120 versus 31%; range 16-64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.

Adult familial cryptogenic fibrosing alveolitis in the United Kingdom.

BACKGROUND: Familial cases of cryptogenic fibrosing alveolitis (CFA) have previously been reported; however, the prevalence and genetic background of this disorder are not known. The clinical and epidemiological findings of 25 families identified within the UK are reported. METHODS: Adult pulmonary physicians in the UK were asked to identify all families under their care in which two or more individuals had been diagnosed with fibrosing alveolitis of unknown cause. A detailed structured questionnaire was sent to each proband to delineate possible environmental/occupational exposures and to obtain complete pedigree data. Physicians were also asked to provide clinical and diagnostic information. RESULTS: Twenty five families were identified comprising 67 cases. Suitable data for analysis were available for 21 families (57 cases). The male:female ratio was 1. 75:1 (p<0.05). A high resolution computed tomographic (HRCT) scan was performed in 93% and a diagnosis of CFA confirmed on biopsy specimens in 32%. The mean age at diagnosis was 55.5 (2.5) years. Fifty percent of cases were ever smokers and 18% had been diagnosed as asthmatic. Exposure to known fibrogenic agents was recorded by 36% of patients. Clinical signs/symptoms and histological findings were indistinguishable from non-familial cases. CONCLUSIONS: This study represents the largest cohort of familial CFA cases reported to date and confirms a prevalence of 1.34 cases per 10(6) in the UK population. Although rare, such cases represent an important subgroup in which a genetic susceptibility to pulmonary fibrosis is particularly evident. Familial patients are younger at diagnosis but otherwise indistinguishable from non-familial cases. The mode of inheritance is as yet unclear but a number of genetic loci are likely to be involved and are the subject of ongoing studies.